Structural analysis of peptide identified from the 2KRR domain of the nucleolin protein with a c-Myc G4 structure using biophysical and biochemical methods.

For the first time, the c-Myc G4 structure is reported to be stabilized by binding of the peptide (derived from the 2KRR domain of the nucleolin protein called the Nu peptide) in the loop region of the G-quadruplex structure by stacking interactions. CD results showed the formation of parallel G4 structure in the presence of 100 mM Na or 100 mM K with the appearance of two isodichroic points at 229 nm, 254 nm and 252 nm in the presence of 100 mM Na or 100 mM K, respectively. In addition, in UV thermal and CD melting studies, we observed drastic changes with an increase in the hyperchromicity at a DNA : peptide ratio of 1 : 50.

Computational methods directed towards drug repurposing for COVID-19: advantages and limitations.

Novel coronavirus disease 2019 (COVID-19) has significantly altered the socio-economic status of countries. Although vaccines are now available against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent for COVID-19, it continues to transmit and newer variants of concern have been consistently emerging world-wide. Computational strategies involving drug repurposing offer a viable opportunity to choose a medication from a rundown of affirmed drugs against distinct diseases including COVID-19.

Significant structural change in human c-Myc promoter G-quadruplex upon peptide binding in potassium.

We selected the G-quadruplex motif located in the nuclease-hypersensitive elements (NHE) III1 region of the c-Myc promoter and for the first time performed its interaction studies with a designed peptide (QW10). Our CD results showed that the peptide bound to the c-Myc G-quadruplex and induced a significant blue shift in the positive peak of 20 nm in KCl alone or with 40wt% PEG200 or 20wt% PEG8000 in comparison to NaCl. Our Native Gel results confirmed that peptide binding destabilized the duplex and stabilized the unimolecular G-quadruplex and not binding to i-motif.

Medicinal chemistry perspectives of 1,2,3,4-tetrahydroisoquinoline analogs - biological activities and SAR studies.

Isoquinoline alkaloids are a large group of natural products in which 1,2,3,4-tetrahydroisoquinolines (THIQ) form an important class. THIQ based natural and synthetic compounds exert diverse biological activities against various infective pathogens and neurodegenerative disorders. Due to these reasons, the THIQ heterocyclic scaffold has garnered a lot of attention in the scientific community which has resulted in the development of novel THIQ analogs with potent biological activity.

Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach.

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor.